Immunogenic and pathogenic subfractions of Coxiella burnetii, the etiological agent of Q fever, are being studied in animals and humans to evaluate humoral and cellular mechanisms of immunity. A. Mice. Phase I whole cell and chloroform-methanol residue vaccines prepared by Salk Institute protected A/J mice from lethal challenge by aerosol and intraperitoneal routes. The aerosol route did not induce antibodies against phase I lipopolysaccharide, yet marked increases of antibody against surface proteins were measured. This surprising result contradicts the traditional view that antibodies against LPSI are a measure of immunity. Therefore protein subunit vaccines may be efficacious. The resistance of C. burnetii to formalin treatment has led to the evaluation of gamma (60Co) dose response to inactivate residual viable organisms in vaccine preparations. One thousand kilo Rads are required to kill 3.8X1010 organisms per ml of medium for the effective sterilization of vaccines and reagents. B. Immune Modulation. The immune suppressive complex (ISC) virulence factor was expressed differently among 9 strains of C. burnetii. Strains expressing only smooth LPSI carried the most potent ISC. None of the strains with only rough LPSII expressed the ISC. However, one strain isolated from heart valve did not expressed the ISC although it contained both smooth and rough LPS chemotypes. C. Antigen Shift. Immuno-gold labeling techniques were used to verify that the different morphologic forms of C. burnetii express different antigenic surfaces. Also the endospore within the large cells were not detected by any antibody preparation. D. Seroepidemiology. A case controlled study to determine the incidence and risk for acquisition of Q fever has revealed that parturient cats are significant in outbreaks of atypical pneumonia. The role of cats in the spread of Q fever to humans may impact significantly of this zoonosis. E. Significance. This project identified a non-toxic efficacious Q fever vaccine, derived a gamma irradiation protocol to kill residual C. burnetii, described different components of the ISC and the distribution among strains, verified antigenic shift among cell variants and defined the role of parturient cats in the spread of Q fever.